Eco-evolutionary dynamics of experimental Pseudomonas aeruginosa populations under oxidative stress

Within-host environments are likely to present a challenging and stressful environment for opportunistic pathogenic bacteria colonizing from the external environment. How populations of pathogenic bacteria respond to such environmental challenges and how this varies between strains is not well understood. Oxidative stress is one of the defences adopted by the human immune system to confront invading bacteria. In this study, we show that strains of the opportunistic pathogenic bacterium Pseudomonas aeruginosa vary in their eco-evolutionary responses to hydrogen peroxide stress. By quantifying their 24 h growth kinetics across hydrogen peroxide gradients we show that a transmissible epidemic strain isolated from a chronic airway infection of a cystic fibrosis patient, LESB58, is much more susceptible to hydrogen peroxide than either of the reference strains, PA14 or PAO1, with PAO1 showing the lowest susceptibility. Using a 12 day serial passaging experiment combined with a mathematical model, we then show that short-term susceptibility controls the longer-term survival of populations exposed to subinhibitory levels of hydrogen peroxide, but that phenotypic evolutionary responses can delay population extinction. Our model further suggests that hydrogen peroxide driven extinctions are more likely with higher rates of population turnover. Together, these findings suggest that hydrogen peroxide is likely to be an effective defence in host niches where there is high population turnover, which may explain the counter-intuitively high susceptibility of a strain isolated from chronic lung infection, where such ecological dynamics may be slower.